Chemo/Immunotherapy Combo for Head and Neck Cancer

Overseen By Jeffrey Kettler

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Systemic immunosuppressants, High-dose steroids

Disqualifiers: CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a chemotherapy and immunotherapy combination for patients with head and neck cancer, specifically squamous cell carcinoma, who cannot use the standard drug 5-fluorouracil. The treatment includes two chemotherapy drugs, carboplatin and paclitaxel, along with the immunotherapy drug pembrolizumab. Suitable candidates have cancer that cannot be cured with radiation or surgery and has either spread or recurred. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have an active autoimmune disease requiring systemic immunosuppression, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of pembrolizumab, carboplatin, and paclitaxel is generally safe. While side effects occur, doctors can usually manage them. In earlier studies, patients with head and neck cancer who received this treatment combination experienced encouraging results.

Reported side effects include tiredness, nausea, and some blood-related issues, mostly mild to moderate. Serious side effects were less common. Pembrolizumab is already known to be relatively safe when used with carboplatin and paclitaxel in other conditions, providing reassurance that the treatment has been studied for safety in humans before.

When considering joining a trial, it's important to know that this treatment is part of a Phase 2 study. This phase tests how well the treatment works and its safety, but previous research suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about this treatment combo because it combines chemotherapy with immunotherapy, offering a fresh approach to fighting head and neck cancer. Most treatments for this condition, like surgery or radiation, target the tumor directly. However, the addition of Pembrolizumab, an immunotherapy drug, helps activate the immune system to recognize and attack cancer cells, potentially improving outcomes. This combination is designed to enhance the effectiveness of conventional chemotherapy drugs like Carboplatin and Paclitaxel, which work by stopping cancer cell growth. By integrating these methods, this treatment has the potential to provide a more comprehensive attack on cancer cells, increasing the chances of remission.

What evidence suggests that this chemo/immunotherapy combo could be effective for head and neck cancer?

Research has shown that a combination of three drugs—pembrolizumab, carboplatin, and paclitaxel—holds promise for treating head and neck cancer. This trial will evaluate this combination therapy, which studies have found can effectively shrink tumors and help control cancer spread in patients with recurring or advanced head and neck cancer. Researchers consider this treatment a top choice for initial therapy because it works well against tumors and has generally manageable side effects. It has also proven safe and effective, making it a good option for those unable to use other common treatments like 5-fluorouracil. ^{1 2 3 6 7}

Who Is on the Research Team?

Thomas Lycan

Principal Investigator

Wake Forest Baptist Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults with advanced head/neck squamous cell carcinoma that can't be cured by surgery or radiation, and who cannot take the drug 5-fluorouracil. Participants need to have a certain level of physical fitness (ECOG 0-2) and adequate organ function. Pregnant women, individuals with untreated brain metastases, severe allergies to chemo drugs used in this study, active autoimmune diseases requiring steroids, or any serious health issues that could interfere with the trial are excluded.

Inclusion Criteria

I cannot receive 5FU treatment due to side effects, practical issues, or personal choice.

My blood tests show normal organ function and healthy blood cell counts.

I can understand and am willing to sign the consent form.

Exclusion Criteria

I have had severe lung inflammation treated with high-dose steroids.

I am on medication to suppress my immune system due to an autoimmune disease.

History of greater than or equal to Grade 3 hypersensitivity reaction to carboplatin or paclitaxel.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive six cycles of pembrolizumab with weekly carboplatin and paclitaxel

18 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests weekly chemotherapy (carboplatin and paclitaxel) combined with immunotherapy (pembrolizumab) on patients with metastatic head/neck cancer who can't receive standard treatment. The goal is to evaluate the effectiveness and safety of this regimen in controlling cancer progression.

How Is the Trial Designed?

Group I: Combination of Chemotherapy and Immunotherapy Experimental Treatment 3 Interventions

The intervention will be administered on an outpatient basis. The treatment regimen will consist of combination chemotherapy and immunotherapy administered as: Pembrolizumab PLUS Carboplatin PLUS Paclitaxel.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

Citations

1. merck.com merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-part-of-a-treatment-regimen-for-adults-with-resectable-locally-advanced-head-and-neck-squamous-cell-carcinoma-la-hnscc-expressing-pd-l1/

European Commission Approves KEYTRUDA® ... In Europe, it is estimated there were approximately 161,900 new cases of head and neck cancer and more than 72,500 deaths from the disease in 2022. These data ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40272712/

Pembrolizumab with Carboplatin and Paclitaxel Versus ... This study aims to estimate the comparative efficacy of KN-B10 versus alternative first-line systemic treatments for R/M HNSCC via an indirect treatment ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02625

Pembrolizumab Plus Carboplatin and Paclitaxel as First- ... Pembrolizumab plus carboplatin and paclitaxel showed promising antitumor activity and a manageable safety profile in first-line R/M HNSCC.

4. keytrudahcp.com keytrudahcp.com/efficacy/hnscc-first-line-combination-therapy/

KEYNOTE-048 - Clinical Trial Results for First-line ... Pembrolizumab (KEYTRUDA) is the ONLY NCCN CATEGORY 1 PREFERRED FIRST-LINE SYSTEMIC THERAPY OPTION for Recurrent, Unresectable, or Metastatic Head and Neck ...

5. onclive.com onclive.com/view/pembrolizumab-plus-chemo-elicits-responses-in-head-and-neck-squamous-cell-carcinoma

Pembrolizumab Plus Chemo Elicits Responses in Head ... The first-line combination of pembrolizumab (Keytruda), carboplatin, and paclitaxel demonstrated antitumor activity and a manageable toxicity profile

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04198766

NCT04198766 | Study of INBRX-106 and ... This is a Phase 1/2, open-label, non-randomized, 4-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended ...

7. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease ...